The A2ALL consortium was chartered in 2002 and has collected data on a large cohort of donor and recipient candidates for LDLT spanning over a decade of activity in 9 US centers. Dr. Emond has been a Co-chair of A2ALL and a member of the Project Executive Committee since the onset of the study and led the development of the cohort protocol. The consortium has contributed important publications defining the benefit of choosing living donation, and the outcomes and complications of the donor and recipient procedure. Descriptive studies from the retrospective cohort have defined the donor evaluation, and illuminated important issues on hepatitis C, HCC, and rejection in recipients of LDLT. A2ALL remains positioned to address critical biological questions related to hepatic inflammation, regeneration, and carcinogenesis in the recipient. A novel and important interventional trial of pre-transplant treatment of HCV in LDLT candidates is underway. Equally important is to study donor liver function and regeneration as well as to define the long-term medical and psychological consequences of liver donation. Columbia has contributed substantially to the overall accrual of A2ALL includes 239 subjects in retro, 17 subjects in bridge and 270 in A2ALL cohort. Clinical outcomes are excellent with a one year recipient survival of 95.3% of adults. In this application for renewal, we commit to continued follow-up of our donors and recipients and further accrual of subjects to achieve the goals of the consortium as defined in the RFA. We describe numerous organizational and technologic improvements in our center, including dedicated staff and an electronic record system to optimize data collection and follow-up. Though A2ALL has made great progress in description of LDLT and defining the outcomes, we have fallen short in two critical areas, understanding of the donor experience and development of surgical innovations to reduce the donor operation without compromising recipient outcomes. These related issues are central to making the case for expansion of LDLT in adults. No matter how good the results of LDLT, there will be no impact if it is not used. To this end we introduce two research proposals that are complementary and enhance the overall aims of A2ALL. First, a structured study of the psychiatric complications in living donors including developing predictors and determining using a control population of concurrently enrolled laparoscopic renal donors whether more limited hepatectomy will improve psychological health of donors. Second, a pilot protocol of using smaller left lobe grafts with appropriate biological and technical manipulations PUBLIC HEALTH RELEVANCE: There remains a major shortage of donors for the nearly 16000 patients waiting for liver transplantation (OLT). Living donor liver transplantation (LDLT) has offered an alternative source of organs but was used in only 178 of 5705 adults (3.1%) receiving OLT in the US in 2008. We propose to increase the use of LDLT by interventions which decrease the extent of the donor hepatectomy, increasing donor safety